Discovery and Characterization of an Acridine Radical Photoreductant

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Nicewicz Research Group - UNC Chapel Hill - 2020 (click for website)

It is no secret that we in the Nicewicz lab have a certain affection for acridinium salts. Since the initial years of the group, these molecules have served as a source of inspiration, joy, and frustration for all members. Across time we have been gradually learning more and more about what makes these catalysts tick and what we can do to get the most mileage out of their photon-absorbing abilities. Acridinium salts are most well-known for their ability to act as strong excited state oxidants – much stronger than typical transition-metal based photoredox catalysts. We have been able to leverage the oxidizing power of acridinium salts to develop a wide variety alkene hydrofunctionalization and aromatic C-H functionalization reactions. Now, we report the discovery and characterization of an acridine radical as an extremely potent photoreductants, out this week in Nature (Nature, 2020, 580, 76-80).

General scheme for photoredox alkene functionalization reactions developed by the Nicewicz lab

In solution, acridinium has a lovely bright yellow color with a dash of green fluorescence under the right lighting. It is a frequent sight and a familiar shade to all members of the lab.  

Photoredox reactions in the Nicewicz lab photoreactor

It wasn’t until graduate student Nathan Romero began investigating the mechanism of our anti-Markovnikov hydrofunctionalization reactions that he and Dave realized that the one electron reduced relative of the acridinium, an acridine radical, may be a very interesting species itself. Interestingly, when Nate added a dash of cobaltocene to reduce the acridinium to the corresponding acridine radical, a deep red-brown coloration quickly appeared – indicating formation of the acridine radical, a one-electron reduced form of the acridinium salt.

Dr. Nathan Romero

Generation of acridine radical

Not only this, but Dave and Nate noticed that samples of the radical could be stored in solution in our glovebox for months at a time without degradation. As one astute member of our lab once said, all it takes to do some photochemistry is to “shine light”. Taking this to heart, the two posed the question “Well, what if we shine light on THAT!”. A few excited whiteboard conversations later, this seemed like a pretty good idea for a rainy day. No one anticipated this simple idea was the catalyst for a two-year long investigation to the powerful chemistry of this species.

Dr. Ian MacKenzie

Ian is a big fan of spectroscopy. In his early career, Ian became very familiar with electron paramagnetic spectroscopy (EPR), an analytical method used for studying free radical species. With his background in odd-electron species, Dave thought that Ian might be just the person to bring this radical idea to fruition. After some initial EPR experiments, Ian found himself inside of the (then) Energy Fuels Research Center at UNC, eagerly adjusting lasers and lenses. It was here that Ian found there was much more to this radical than meets the eye (or the detector). Ian dove headfirst into explorations of the excited state chemistry of the acridine radical. A few measurements later, Ian came up with an interesting result: This radical is an extremely potent reductant. Simply by switching out our typical blue 455 nm LED lamps for purple 390 nm LED lamps, Ian discovered this radical had a maximum excited state reducing ability comparable to metallic lithium! This was certainly unexpected for a molecule we had grown to known so well as an oxidant. Together Ian and post-doc Leifeng went on to investigate the catalytic competence of this radical, developing methods for the dehalogenation of electron-rich aromatics and detosylation of amines – reactions typically requiring harsh stochiometric reductants. Indeed, spectroscopic measurements confirmed that 390 nm irradiation was required for the population of higher energy excited states.

Dr. Leifeng Wang

As Ian began preparing to graduate, I (Nick) joined the project and began to think about how we might make sense of this wild reactivity! It didn’t take long before I realized that I would need a little bit of help from some colleagues, both near and far. Transient absorption spectroscopy is a fascinating method for uncovering electronic structure and dynamics on incredibly short (picosecond) time scales – just the type of technique we needed to employ to examine the excited state behavior of this radical. Fortunately, it was not difficult to find experts on the subject in our colleagues of the Moran lab at UNC - just a short trip down an elevator.  Together, Olivia Williams, a graduate student in the Moran lab, and I got to work to figure out the rest of this story. Several careful executions of glovebox slight-of-hand afforded a cuvette full of radical that was ready to study. Once Olivia carefully calibrated the laser table and pulsed the sample, we observed a variety of red-shifted resonances corresponding to the excited state of the radical. Having studied the charge transfer complexes of analogous acridinium salts, we speculated charge transfer processes may be at play in this system as well.

Dr. Andrew Moran (left) and Olivia Williams (right)

It was time to bring in some more collaborators – this time from my own undergraduate institution of Kent State University! Prof. Barry Duneitz and graduate student Khadiza Begam – both experts in time-dependent density functional theory calculations - graciously accepted our invitation to collaborate in studying the excited state behavior of the acridine radical. Khadiza and Barry were able to use their innovative screened range separated hybrid (SRSH) functional to help us in calculating excited state energies and examining the electron density of these fleeting species in exquisite detail. The methods their group has developed are particularly useful for examining state energies of solvated donor-acceptor complexes and have proven useful in analyzing the spectral trends of pigments with increased accuracy where conventional TD-DFT calculations fail. Indeed, calculations confirmed that our initial spectroscopic measurements were accurate – this radical possesses a maximum excited state oxidation potential of  -3.36 V v. SCE! Furthermore, orbital density maps generated by Khadiza confirmed our suspicion that this chemistry may rely on the formation of charge transfer excited states, supporting the data we collected with the Moran lab at UNC. In contrast to charge transfer species associated with acridinium salts, the radical charge transfer state seems to involve charge transfer to the N-phenyl ring of the molecule, rather than the mesityl group.

Going forward, we anticipate that this discovery will help to propel the rapidly expanding field of reductive photoredox catalysis and serve as the conceptual basis for the development of other families of highly reducing catalysts.

General scheme of acridinium/acridine radical photochemistry



Nicholas Onuska

PhD Candidate, University of North Carolina - Chapel Hill


Go to the profile of Ian MacKenzie
almost 2 years ago

Awesome summary Nick! It was a ton of fun to work on this project with you.